3,5-Dibromopyridine → [2-(5-Bromopyridin-3-yl)-2-azabicyclo[3.1.0]hex-3-yl]methanol

Temperature

110 °C

To a stirred solution of (2-Azabicyclo[3.1.0]hex-3-yl)methanol (750 mg, 6.63 mmol) (obtained in step (i)) in dry 1,4-dioxan (20 mL) in a pressure reaction vessel was added 3,5-dibromopyridine (1.57 grams, 6.63 mmol), sodium tert-butoxide (700 mg, 7.3 mmol) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (207 mg, 0.33 mmol). The reaction mixture was degassed for 30 minutes, then tris(dibenzylideneacetone)dipalladium (0) (122 mg, 0.133 mmol) was added. The screw cap was fixed on the reaction vessel, the temperature of the reaction was gradually increased to 110° C. and the reaction mixture was stirred at this temperature for 16 hours. The reaction mixture was cooled to room temperature diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure and the crude product was purified by 230-400 silica gel flash column chromatography to obtain title compound of 600 mg as solid. Yield: 33%.

1. customThe reaction mixture was degassed for 30 minutes
2. customThe screw cap
3. temperatureThe reaction mixture was cooled to room temperature
4. extractionextracted with ethyl acetate
5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
6. customthe solvent was removed under reduced pressure
7. customthe crude product was purified by 230-400 silica gel flash column chromatography

ORD record

ord-e28703a6b21743028431e44ce439ac68

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653071B2